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Multicenter Study
. 2022 Jul;77(1):84-97.
doi: 10.1016/j.jhep.2022.01.022. Epub 2022 Feb 8.

Risk factors and outcomes associated with recurrent autoimmune hepatitis following liver transplantation

Aldo J Montano-Loza  1 , Vincenzo Ronca  2 , Maryam Ebadi  3 , Bettina E Hansen  4 , Gideon Hirschfield  4 , Saleh Elwir  5 , Mohamad Alsaed  5 , Piotr Milkiewicz  6 , Maciej K Janik  6 , Hanns-Ulrich Marschall  7 , Maria Antonella Burza  7 , Cumali Efe  8 , Ali Rıza Calışkan  9 , Murat Harputluoglu  9 , Gökhan Kabaçam  10 , Débora Terrabuio  11 , Fernanda de Quadros Onofrio  4 , Nazia Selzner  4 , Alan Bonder  12 , Albert Parés  13 , Laura Llovet  13 , Murat Akyıldız  14 , Cigdem Arikan  15 , Michael P Manns  16 , Richard Taubert  16 , Anna-Lena Weber  16 , Thomas D Schiano  17 , Brandy Haydel  17 , Piotr Czubkowski  18 , Piotr Socha  18 , Natalia Ołdak  18 , Nobuhisa Akamatsu  19 , Atsushi Tanaka  20 , Cynthia Levy  21 , Eric F Martin  21 , Aparna Goel  22 , Mai Sedki  22 , Irena Jankowska  23 , Toru Ikegami  24 , Maria Rodriguez  25 , Martina Sterneck  25 , Christina Weiler-Normann  25 , Christoph Schramm  25 , Maria Francesca Donato  26 , Ansgar Lohse  27 , Raul J Andrade  28 , Vilas R Patwardhan  12 , Bart van Hoek  29 , Maaike Biewenga  29 , Andreas E Kremer  30 , Yoshihide Ueda  31 , Mark Deneau  32 , Mark Pedersen  33 , Marlyn J Mayo  33 , Annarosa Floreani  34 , Patrizia Burra  34 , Maria Francesca Secchi  35 , Benedetta Terziroli Beretta-Piccoli  36 , Marco Sciveres  37 , Giuseppe Maggiore  38 , Syed-Mohammed Jafri  39 , Dominique Debray  40 , Muriel Girard  40 , Florence Lacaille  41 , Ellina Lytvyak  3 , Andrew L Mason  3 , Michael Heneghan  42 , Ye Htun Oo  43 ; International Autoimmune Hepatitis Group (IAIHG)
Affiliations
Free article
Multicenter Study

Risk factors and outcomes associated with recurrent autoimmune hepatitis following liver transplantation

Aldo J Montano-Loza et al. J Hepatol. 2022 Jul.
Free article

Abstract

Background & aims: Autoimmune hepatitis can recur after liver transplantation (LT), though the impact of recurrence on patient and graft survival has not been well characterized. We evaluated a large, international, multicenter cohort to identify the probability and risk factors associated with recurrent AIH and the association between recurrent disease and patient and graft survival.

Methods: We included 736 patients (77% female, mean age 42±1 years) with AIH who underwent LT from January 1987 through June 2020, among 33 centers in North America, South America, Europe and Asia. Clinical data before and after LT, biochemical data within the first 12 months after LT, and immunosuppression after LT were analyzed to identify patients at higher risk of AIH recurrence based on histological diagnosis.

Results: AIH recurred in 20% of patients after 5 years and 31% after 10 years. Age at LT ≤42 years (hazard ratio [HR] 3.15; 95% CI 1.22-8.16; p = 0.02), use of mycophenolate mofetil post-LT (HR 3.06; 95% CI 1.39-6.73; p = 0.005), donor and recipient sex mismatch (HR 2.57; 95% CI 1.39-4.76; p = 0.003) and high IgG pre-LT (HR 1.04; 95% CI 1.01-1.06; p = 0.004) were associated with higher risk of AIH recurrence after adjusting for other confounders. In multivariate Cox regression, recurrent AIH (as a time-dependent covariate) was significantly associated with graft loss (HR 10.79, 95% CI 5.37-21.66, p <0.001) and death (HR 2.53, 95% CI 1.48-4.33, p = 0.001).

Conclusion: Recurrence of AIH following transplant is frequent and is associated with younger age at LT, use of mycophenolate mofetil post-LT, sex mismatch and high IgG pre-LT. We demonstrate an association between disease recurrence and impaired graft and overall survival in patients with AIH, highlighting the importance of ongoing efforts to better characterize, prevent and treat recurrent AIH.

Lay summary: Recurrent autoimmune hepatitis following liver transplant is frequent and is associated with some recipient features and the type of immunosuppressive medications use. Recurrent autoimmune hepatitis negatively affects outcomes after liver transplantation. Thus, improved measures are required to prevent and treat this condition.

Keywords: autoimmune liver disease; graft survival; liver transplantation; recurrent disease; survival.

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Conflict of interest statement

Conflicts of interest These authors disclose the following: A.J. Montano-Loza has served on advisory boards for Intercept Pharmaceuticals. B.E. Hansen reports grants from Intercept Pharmaceuticals and Zambon Nederland B.V. and consulting work for Intercept Pharmaceuticals and Novartis. A.E. Kremer reports consulting work for CymaBay, GSK, Intercept Pharmaceuticals, and Mirum and grants from Intercept Pharmaceuticals. A. Parés consults for Intercept and Novartis. A. Floreani reports consulting activities for Intercept Pharmaceuticals. A. Mason consults for, is on the speakers' bureau of, and received grants from Intercept. He received grants from Merk. The remaining authors disclose no conflicts. Please refer to the accompanying ICMJE disclosure forms for further details.

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